Lubiprostone is an active pharmaceutical ingredient in the drug product Amitiza® for the treatment of diseases such as chronic idiopathic constipation, predominantly irritable bowel syndrome-associated constipation in women and opioid-induced constipation. Currently available methods for the synthesis of Lubiprostone disclosed in the prior art, such as in EP 0430551, U.S. Pat. Nos. 7,812,182, 7,928,252, 8,309,744, 9,382,272, and CN 103787942, use Corey lactone or derivatives thereof as a starting material to respectively construct the α-side chain and the ω-side chain of Lubiprostone by a two-step Wittig reaction as shown in the following Scheme A. However, the Corey method requires many synthetic steps and thus results in low yield.

As shown in the following Scheme B, Lubiprostone disclosed in the prior art, such as in U.S. Pat. No. 9,670,234 and WO 2012048447, is synthesized by 1,4-conjugate addition of cyclopentenone A and a vinylboron compound or vinyl caprate B to form Lubiprostone's intermediate C with double bonds at C13-C14, C5-C6, and/or C17-C18; removing the benzyl protecting group through hydrogenation and reducing the double bonds at C13-C14, C5-C6, and/or C17-C18 to single bonds to give compound D; and carrying out three additional chemical reactions.

This process can more rapidly form Lubiprostone. However, due to huge steric hindrance on both sides of the double bond at C13-C14, the intermediate C is very difficult to be hydrogenated or reduced. A large amount of expensive hydrogenation catalysts must be used under high pressure and high temperatures to reduce all the double bonds to single bonds. In these circumstances, by-products are inevitably produced due to incompletely reduced double bonds, and dehydration or deoxygenation by-products or even by-products with shifted double bonds are also generated due to extreme conditions. Since these by-products are similar to the main products with single bonds in polarity, it is almost impossible to completely remove the hydrogenation by-products by using a silica gel chromatography method. Therefore, the industrial purification of Lubiprostone in mass production has encountered great difficulties.
Consequently, there is a demand for efficient and economical processes for the preparation of Lubiprostone with high yield and high purity.